Thiamine Supplementation in Patients with Chronic Heart Failure Receiving Optimum Medical Treatment

Abstract

Background: Thiamine deficiency may cause heart failure and symptoms including edema, palpitation, tachycardia, weakness, malaise, and dyspnea due to water and salt retention and peripheral vasodilation. Patients with heart failure might be thiamine deficient and benefit thiamine supplementation. This study was designed to evaluate the effect of thiamin supplementation on some systolic and diastolic echocardiographic parameters and signs and symptoms of heart failure.Methods: Fifty two patients with systolic heart failure (LVEF < 40%) receiving optimum medical treatment, were randomized to receive 300mg thiamine or placebo for 1 month in a double-blind fashion (26 patients in each group). Echocardiographies were performed before and after treatment by a single investigator and sign and symptoms were evaluated (clinicaltrials.gov Identifier # NCT01115504). Results:Mean age was 61.44 ± 11.8 years and 67.3% were male. Maximal systolic tissue velocity of of septal and lateral walls (Sm waves) increased 0. 99 ± 1.46 and 0.83 ± 1.58 cm/s in thiamine group and changed 0.005± 1.63 and -0.1 ± 1.83 cm/s in placebo group (P = 0.033 and P = 0.044) respectievely. Ejection fraction or diastolic echocardiographic parameters were not influenced by thiamine supplementation and there was no significant effect on daily activities and dyspnea. However, peripheraledema improved in 9 patients (34.6%) of thiamine group versus 1 of the placebo group (3.8%) (P = 0.005). Conclusion:In the present study thiamine supplementation had some positive effect on edema and systolic function through an increase of lateral and septal Sm. However usefulness of routine supplementation needs more study Keywords: Thiamine; Heart failure; Edema; Signs and Symptoms, regimen of the patients in the past 3 months, due to aggravated symptoms or optimization of dosage for a survival benefit according to the present guidelines. Excluded patients were those with decompensated heart failure, bradycardia or tachycardia (needing a change in drug dosage or regimen), concomitant medical illness e.g. chronic renal failure, chronic obstructive pulmonary disease, asthma and uncontrolled hypertension.The study was a single-site randomized placebo-controlled double blind trial and enrolled patients were randomized by means of block randomization method by a single pharmacist. Patients were assigned to randomly receive 300mg daily of thiamine (HakimVitamin B1300®, Hakim pharmaceutical industry, Tehran, Iran) (n=26, thiamine group) or placebo (Hakim pharmaceutical industry, Tehran, Iran) (n=26, placebo group) for 30 days in a double-blind fashion.At randomization and at the end of study, echocardiography (Sonace 8000 EX, South Korea) was performed by a single operator in a blinded fashion. Ejection fraction was measured in 2D echocardiography in apical 4 chamber and apical 2 chamber views by means of Simpson method. Maximal systolic velocity of myocardial tissue of septal and lateral walls (Sm waves) were obtained by tissue Doppler imaging of lateral and septal wal...

High-Dose Thiamine Supplementation in Older Patients With Heart Failure: A Pilot Randomized Controlled Crossover Trial (THIAMINE-HF)

“…In this pilot trial of thiamine supplementation in older adults with HFrEF, we were unable to recruit the target number of patients within 11 months, but our other feasibility targets were reached, including retention, refusal, and adherence rates. Similar to a recent parallel group thiamine trial [8], our study did not identify statistically significant benefits of thiamine supplementation, despite using a higher daily dose (500mg) than previous trials (100-300mg) [7,8,[19][20][21]. The use of sensitive markers such as peak GLS on echocardiography and NT-proBNP reveal non-significant improvement with supplementation over 3 months.…”

“…A meta-analysis of two small placebo-controlled trials (pooled n=38) showed a small improvement (absolute increase of 3.28%, 95% confidence interval [CI] 0.64-5.93) in left ventricular ejection fraction (LVEF) with thiamine doses of 200-300mg/day [6]. Another trial of 50 stable HFrEF patients (mean age 61.4 years) showed no change to LVEF after 1 month of thiamine supplementation (300mg/day), but there was an improvement in patient-reported peripheral edema [7]. A recent trial of 69 stable HFrEF patients (mean age 56.7 years) found no changes in LVEF and NT-proBNP after 6 months of thiamine supplementation (200mg/day) [8].…”

“…Older adults aged ≥65 years are more susceptible to thiamine deficiency [4], and may be more likely to benefit from thiamine supplementation. The two negative trials of thiamine supplementation did not enrich their sample for older age [7,8]. In addition, older adults are often underrepresented in randomized trials of pharmacologic agents in HF as they may not tolerate the target doses of HF medications or may have comorbidities that lead to exclusion [9].…”

Metabolic Therapy of Heart Failure: Is There a Future for B Vitamins?

“…Whereas the trial led by Seligmann et al in the nineties showed that the beneficial effect of thiamine on left ventricular ejection fraction was associated with better functional capacity (improved by at least one NYHA class) [ 153 ], it was confirmed in a more recent study by Schoenenberger et al in which no change in walking time was observed in patients with improved left ventricular ejection fraction after thiamine supplementation period [ 165 ]. This raises questions about the real usefulness of thiamine supplementation in HF therapy, especially as other trials failed to demonstrate any benefit of vitamin B1 (dose ranging from 100 mg to 300 mg per day) although thiamine circulating level increased [ 15 , 166 , 167 , 168 ]. These studies not only failed to show a beneficial effect on cardiac function (FE) [ 15 , 167 ] but also failed to show an improvement in the quality of life of HF patients [ 15 , 166 , 167 , 168 ].…”

“…This raises questions about the real usefulness of thiamine supplementation in HF therapy, especially as other trials failed to demonstrate any benefit of vitamin B1 (dose ranging from 100 mg to 300 mg per day) although thiamine circulating level increased [ 15 , 166 , 167 , 168 ]. These studies not only failed to show a beneficial effect on cardiac function (FE) [ 15 , 167 ] but also failed to show an improvement in the quality of life of HF patients [ 15 , 166 , 167 , 168 ]. So far, the evaluation of thiamine supplementation as a new tool in HF therapeutics has shown mixed results and conclusions from the aforementioned studies are not clear because of the small sample size, short duration of follow-up, lack of any dietary assessment of thiamine intake, as well as the lack of precisely defined inclusion criteria.…”